The present invention relates to devices and methods for entrapping gas in liquid drug containers, and in particular relates to drug cartridges and stoppers for filling drug delivery devices, and methods relating to such filling.
For reasons of stability and accuracy of delivery it is often desired to store a liquid drug in a container such as a standard drug cartridge. Such cartridges may typically be cylindrical and be sealed at an open end by a penetrable stopper or piston. To release the drug, the stopper is typically punctured by a hollow needle and then moved along the length of the container whereupon it acts as a piston to pump liquid drug from the container through the needle. Such cartridges are typically used in pre-filled syringes of the type manufactured by IMS of So. El Monte, Calif., U.S.A. and by Abbott Laboratories of N. Chicago, Ill., U.S.A. and also in the infusion system, which is the subject of WO 95/13838.
If any air or gas is present in the cartridge after it is sealed with the stopper, then air or gas may be transferred from the cartridge with the drug. For systems applied by trained personnel (e.g. nurses and doctors) the air can be eliminated through appropriate orientation. However when such systems are used by patients and untrained caregivers there is a danger that the safety may be affected. There are several safety risks associated with air bubbles getting into an infusion pump, syringe or the like. For example, if there is a volume of air delivered via a drug delivery device, then all of the prescribed volume of drug may not be delivered.
Overall accuracy of drug delivery may also be affected when air or other gas is transferred into a drug delivery system. If some of the drug cartridge volume is taken up by air or gas rather than liquid drug, then the prescribed amount of liquid drug is not being delivered to the patient. In cases where the drug being delivered has a narrow therapeutic window, if that window is exceeded due to an air bubble obstruction in the pathway of the drug delivery device, exceeding the window may result in undesirable deleterious side effects. Drugs in this category include aminoglycosides such as Amikacin, Gentamicin, Kanamycin and tobramycin.
In addition to the problem of air bubble obstruction, a volume of air or gas in the drug cartridge may result in a decreased volume of drug delivered. Patients that require drugs that have extremely accurate dosing regimes may suffer if the volume of drug delivered is inaccurate due to the excess volume of gas in the cartridge. Pediatric and geriatric patient groups are typically more sensitive to such dose administrations.
If the drug is a painkiller, such as morphine, extreme suffering will be caused to the patient due to a cessation of drug delivery. In addition, in the case of intravenous delivery, air bubbles may pass into the user""s blood system and obstruct blood flow, thereby causing serious injury and possibly death.
Experience has shown that the manufacturers and fillers of drug cartridges are unable to eliminate air or other gas entirely from their drug cartridges, and for a relatively small volume (5 ml) cartridge, it has not been possible to reduce the amount of air or other gas present to below 25 xcexcl. Typical volumes of gas are in the 100 to 300 xcexcl range.
Moreover, most drug cartridges are filled under sterile conditions and via automatic machinery. Thus, any improvement to the standard drug cartridge that would entrap gas therein and prevent from passing through to a drug delivery device must be able to comply with existing filling and assembly machinery presently used in the industry.
Thus, there is a need for a drug cartridge assembly that entraps gas therein and prevents it from being transferred with liquid drug to a drug delivery device.
There is a further need for a drug cartridge assembly that increases patient safety by preventing any gas from being transferred to a drug delivery device.
There is still a further need for a drug cartridge assembly that increases dosage accuracy in liquid drug delivery via a drug delivery device by preventing any gas from being transferred to such drug delivery device.
There is yet a further need for a stopper that can be used in connection with a standard drug cartridge that entraps gas between the drug cartridge and stopper and prevents it from being transferred with liquid drug to a drug delivery device.
There is a further need for a stopper used in connection with a standard drug cartridge that increases patient safety by preventing any gas transferred from the cartridge to a drug delivery device.
There is still a further need for a stopper used in connection with a standard drug cartridge that increases dosage accuracy in liquid drug delivery via a drug delivery device by preventing any gas from being transferred from the drug cartridge to such drug delivery device.
There is a further need for a method for entrapping gas within a liquid drug container that prevents such gas from being transferred with liquid drug to a drug delivery device.
There is yet a further need for a stopper, used in connection with a standard drug cartridge that prevents gas from being transferred to a drug delivery device, designed for use in presently existing filling and assembly machinery.
There is still a further need for a drug cartridge that prevents gas from being transferred to a drug delivery device, designed for use in presently existing filling and assembly machinery.
The present invention solves the problems associated with the prior art devices and methods by providing for a stopper for use in preventing any volume of gas from escaping from a drug container when used in connection therewith. The stopper comprises a body having a perimeter for slidable engagement with the interior of a drug receptacle, an outer surface, and an inner surface facing the bottom of the drug receptacle. The inner surface is shaped so as to trap any volume of gas located within the drug receptacle when the body is slidably engaged therein.
Such geometries of stopper and/or container create a natural space to trap any gas away from the outlet, as will be described in further detail below.
The inner surface of the stopper is preferably convex, and in particular may be conical, or frusto-conical. The body of the stopper is preferably circular in cross-section.
The stopper may further include an outlet. The outlet connects the inner surface with the outer surface. The outlet is preferably aligned along the longitudinal axis of the stopper. The outlet may be created by penetrating the stopper. The outlet may comprises a hollow needle extending through the inner and outer surfaces of the stopper. This helps ensure sterility of the liquid drug by preventing any interference with the drug between the filling of the container and the emptying thereof.
A second embodiment of the present invention is directed to a liquid drug container. The container includes a hollow body for holding a liquid. The body has an open end and a closed end. The container also includes a stopper slidably received in the hollow body, and means for entrapping a predetermined volume of gas within the container.
Preferably, the hollow body is substantially cylindrical in form and the stopper is of substantially circular cross-section to make a sealing sliding fit with the internal bore of the cylindrical hollow body.
Suitably, the means for preventing exit of gas and entrapping the gas comprises a convex, conical or frusto-conical liquid-facing surface provided on the stopper. Preferably, the entrapping means is located along the perimeter of the stopper. Alternatively, the means for preventing exit of gas and entrapping the gas comprises a convex, conical or frustoconical surface provided on an internal end surface of the substantially cylindrical hollow body facing the stopper.
The container may further include an outlet associated with the stopper through which drug is expelled. Preferably, the outlet is located along the central longitudinal axis of the stopper. For example, the outlet can be a narrow axial bore having a needle or a conduit extending therefrom. Preferably, in such cases, the outlet is created in use by penetrating the stopper. This helps ensure sterility of the liquid drug by preventing any interference with the drug between the filling of the container and the emptying thereof.
When the stopper has slidably moved to the closed end of the hollow body, the gas volume in the container is entrapped away from the outlet. The container is designed to prevent any volume of gas from exiting through the outlet and the gas is entrapped within the container regardless of orientation of the body. Preferably, the outlet is sealed when the stopper reaches the limit of its travel.
The container may further include means for limiting the travel of the stopper. Such means may be external to the hollow body. The container may also include means for slidably moving the stopper within the hollow body. The container may further include means for limiting the travel of the stopper. Such means may be made up of co-operating surfaces on the hollow body and on the means for slidaby moving the stopper within the hollow body.
In further preferred embodiments, the outlet comprises a needle extending partially into the interior of the container through a wall of the container facing the stopper, so as to provide the means for preventing exit of gas and entrapping the gas in the container, the needle limiting the travel of the stopper, thereby forming the entrapment space. The needle may enter the hollow body through either the stopper or a wall of the hollow body.
The present invention is also directed to a position independent method of emptying a liquid drug container while retaining any volume of gas within the container. The method includes the steps of providing a hollow body having an open end and a closed end, the body having liquid drug contained therein, closing the open end of the body with a stopper slidably received within the hollow body at the open end to prevent liquid drug from escaping therefrom. The method further includes the steps of creating an outlet through the longitudinal axis of the stopper through which the liquid drug may be expelled, providing a space between the stopper and the closed end of the body for occupation by any volume of gas within the body, moving the stopper from the open end to the closed end of the body, thereby causing the volume of liquid drug to be expelled from the body via the outlet and, when the stopper completes its travel to the closed end of the hollow body, forcing any volume of gas remaining therein to be located in the space thus preventing the volume of gas from escaping from the body via the outlet.
The step of moving the stopper may be accomplished by causing the stopper to slide along its longitudinal axis within the hollow body. The outlet may be created by extending a hollow needle through the stopper and into the interior of the container.
The use of a volume of gas or an gas trap has been found to eliminate problems associated with the transfer of residual gas trapped in drug containers. It ensures that a small and possibly variable amount of gas, which may become entrapped during the filling process (which in fact is practically impossible to avoid), is never ejected because the container is designed to retain a small amount of liquid drug which would include any entrapped gas when the container is essentially empty. Accordingly, containers according to the invention are designed to ensure that only liquid is expelled by movement of the stopper, and because the dimensions of the stopper and the hollow body can be precisely controlled, it is possible to ensure highly accurate delivery volumes.
This design of container allows the container to be used (e.g. in filling a portable infusion pump) by persons having no training. Whereas a certain degree of training and experience is required to prevent gas contained in a syringe from being transferred to the patient""s tissue or bloodstream. The container according to the invention automatically traps and retains the gas away from the outlet.
The design of the container and of the stopper are also conducive for use with existing automated filling machinery. The stopper and container of the present invention are of the proper exterior dimensions for use in connection with presently available filling and assembly equipment. Thus, there is no need for any retro-fitting or replacement of such machinery.
Other objects, features and advantages of the present invention will become apparent upon reading the following detailed description of the embodiments of the invention when taken in conjunction with the drawings and the appended claims.